Transdiagnostic features of inflammatory markers and executive function across psychiatric disorders

Executive dysfunction and dysregulated inflammation are found in patients with different psychiatric disorders. However, whether there are different associations between inflammatory markers and executive performance in patients with different psychiatric diagnoses is unknown. Our study aims were (1) to compare peripheral cytokine expression and executive function in patients with bipolar disorder (BD), substance use disorder (SUD), and schizophrenia (SCZ), and in healthy controls (HC) and (2) to explore the potential association between inflammatory cytokines and executive function in different patient groups and HC. Participants with BD (n = 816), SUD (opioid use disorder and/or methamphetamine use disorder, n = 518), SCZ (n = 146), and HC (n = 186) were recruited. Plasma cytokine levels [tumor necrosis factor (TNF)-α, interleukin (IL)-8 (only measured in 8 SCZ patients), transforming growth factor (TGF)-β1 (not measured in SCZ patients)], C-reactive protein (CRP), brain-derived neurotrophic factor (BDNF) levels, and executive function [Wisconsin Card Sorting Test (WCST) and Continuous Performance Test (CPT)] were assessed. We found that all patient groups had worse executive performance and higher inflammatory cytokine levels than the HC group. SCZ patients had the worst executive performance, while SUD patients had the highest inflammatory cytokine levels. Increased plasma IL-8, CRP, and TNF-α levels were specifically associated with worse executive function in BD, SUD, and SCZ patients (P = 0.009, 0.04, and 0.03, respectively). We concluded that dysregulated inflammation might be a transdiagnostic feature among different psychiatric disorders and associated with executive dysfunction. Further studies to investigate the causal relationship and mechanisms between inflammation and executive dysfunction may be needed.